Bacteria are ubiquitous, ecologically diverse, and find unusual niches for survival. They are present throughout the environment, e.g., soil, dust, water, and on virtually all surfaces.
Pathogenic bacteria can cause infectious diseases in humans, other animals, and plants. Some bacteria can only infect or cause problems for a particular host, while others have a broader host specificity, and can cause trouble in a number of hosts. Diseases caused by bacteria are almost as diverse as the bacteria themselves, e.g., food poisoning, tooth decay, anthrax, general infectious diseases, and even certain forms of cancer.
Certain bacteria are normally innocuous, but become pathogenic at the appropriate opportunity, or become problematic upon introduction to an abnormal site or situation. Persons lacking effective immune systems are most vulnerable, and certain bacteria use weakened hosts to proliferate and disperse throughout the population.
Antibiotics have revolutionized clinical medicine over the last half century. Since the original discovery of antibiotic phenomenon, the mechanism of action and development of this class of remarkable therapeutic entities has made enormous progress. See e.g., Therrien and Levesque (2000) FEMS Microbiol Rev. 24:251-62: Durgess (1999) Chest 115(3 Suppl):19S-23S; Medeiros (1997) Clin. Infect. Dis. 24(Suppl 1):S19-45; Jones (1996) Am. J. Med. 100(6A):3S-12S; Ford and Hait (1993) Cytotechnology 12(1-3):171-212; and Liu (1992) Compr Ther 18:35-42. Antibiotics had about $32B worldwide sales in 2002.
Yet the widespread appearance of antibiotic-resistant bacteria has emphasized the vulnerability of current antimicrobial treatments to bacterial adaptation. See, e.g., Walsh (1992) Antibiotics: Actions, Origins, Resistance Amer. Soc. Microbiol.; Cunha (1992) Antibiotic Essentials (Physicians Press); Amyes (2003) Magic Bullets, Lost Horizons: The Rise and Fall of Antibiotics (Taylor & Francis); Axelsen (2001) Essentials of Antimicrobial Pharmacology: A Guide to Fundamentals for Practice (Humana Press); and Mainous and Pomeoy (eds. 2001) Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic Resistance (Humana Press). Multiple resistance plasmid NDM-1 has been reported (Kumarasamy et al. (2010) Lancet Infectious Diseases 10:597-602; and Walsh et al. (2011) Lancet Infectious Diseases, Early Online Publication, 7 Apr. 2011, doi:10.1016/S1473-3099(11)70059-7).
Thus, improved methods for decreasing bacterial growth and survival, or limiting bacterial pathogenicity, find great utility, especially for antibiotic resistant bacteria, which are most commonly Gram-negative. Antimicrobial effects are applicable to environmental, local, topical, and particularly in vivo colonization. The present invention addresses these and other significant issues.